Fluoroquinolone preventive therapy for children exposed to MDR-TB.

No Abstrac

Clinical standards for the assessment, management, and rehabilitation of post-TB lung disease

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR). METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement). RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR. CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD

Treatment outcomes in global systematic review and patient meta-analysis of children with extensively drug-resistant tuberculosis

Extensively drug-resistant tuberculosis (XDR TB) has extremely poor treatment outcomes in adults. Limited data are available for children. We report on clinical manifestations, treatment, and outcomes for 37 children (<15 years of age) with bacteriologically confirmed XDR TB in 11 countries. These patients were managed during 1999–2013. For the 37 children, median age was 11 years, 32 (87%) had pulmonary TB, and 29 had a recorded HIV status; 7 (24%) were infected with HIV. Median treatment duration was 7.0 months for the intensive phase and 12.2 months for the continuation phase. Thirty (81%) children had favorable treatment outcomes. Four (11%) died, 1 (3%) failed treatment, and 2 (5%) did not complete treatment. We found a high proportion of favorable treatment outcomes among children, with mortality rates markedly lower than for adults. Regimens and duration of treatment varied considerably. Evaluation of new regimens in children is required

Treatment and outcomes in children with multidrug-resistant tuberculosis: a systematic review and individual patient data meta-analysis.

CAPRISA, 2018.Abstract available in pdf

A comparison between passive and active case finding in TB control in the Arkhangelsk region

Background: In Russia, active case finding (ACF) for certain population groups has been practiced uninterruptedly for many decades, but no studies comparing ACF and passive case finding (PCF) approaches in Russia have been published. Objective: The aim of this study was to describe the main differences in symptoms and diagnostic delay between patients who come to TB services through PCF and ACF strategies. Methods: A cross-sectional study was conducted among 453 new pulmonary tuberculosis (PTB) patients, who met criteria of TB diagnostic delay in Arkhangelsk. Results: ACF patients used self-treatment more often than PCF patients (90.1% vs. 24.6%) and 36.3% of them were alcohol abusers (as opposed to only 26.2% of PCF patients). The median patient delay (PD) in PCF was 4 weeks, IQR (1–8 weeks), and less than 1 week in ACF. Twenty-three per cent of the PCF patients were seen by a medical provider within the first week of their illness onset. Conclusion: Patients diagnosed through ACF tended to under-report their TB symptoms and showed low attention to their own health. However, ACF allowed for discovering TB patients earlier than PCF, and this was also the case for alcohol abusing patients. PCF systems should be supplemented with ACF strategies

Incidence of Tuberculosis and Associations with Indicators of Alcohol Consumption in Three Regions of Northwest Russia in 1975–2009: A Time-Series Analysis

Background. Alcohol has several social consequences that are associated with increased risk of tuberculosis. However, there have been no studies assessing the links between tuberculosis and alcohol consumption in northwest Russia. The aim of this study was to assess associations between the incidence of tuberculosis and indicators of alcohol consumption in three regions of northwest Russia. Methods. The study was performed in Arkhangelsk, Murmansk and Vologda regions using the data from 1975 to 2009. Deaths from alcohol poisoning and the incidence of alcohol psychoses were used as indicators of alcohol consumption. Associations between the incidence of tuberculosis and the above mentioned indicators were studied using time-series analysis. Results. We identified significant positive associations between the incidence of tuberculosis and the incidence of alcohol psychoses in the same year in Arkhangelsk region (β=0.24, 95% CI: 0.10–0.37) and in Vologda region (β=0.18, 95% CI: 0.10–0.25), but not in Murmansk region. Conclusions. We found an association between the incidence of alcohol psychoses and the incidence of tuberculosis in the same year in Arkhangelsk and Vologda regions suggesting an indirect link between excessive levels of alcohol consumption and the incidence of tuberculosis in Russia

Prevention of bronchial fistulas after pneumonectomies for selected cavitary drug resistant lung tuberculosis

Background: The World Health Organization guidelines for management drug resistant tuberculosis include surgery as an additional method in selected cases. Pneumonectomies have higher risk of morbidity such as bronchial fistulas which may be prevented by bronchial stump covering. We compare two methods of bronchial stump reinforcement. Methods and materials: A retrospective single center follow-up study was done in 52 patients who underwent pneumonectomy for drug resistant pulmonary tuberculosis. Between 2000 and 2017 we performed pneumonectomies with pericardial fat reinforcement of bronchial stump in group 1 (n = 42), and between 2017 and 2021 in group 2 with pedicled muscle flap reinforcement group 2 (n = 10). Results: Bronchial fistulas occurred in 17/42 (41%) of patients group 1 and there was no fistula in group 2, and this was statistically different (Fisher's test p = 0.02). Post-operative complications were seen in 24/42 (57%) of the patients in Group 1, and 4/10 (40%) patients in Group 2 (Fischer's test p = 0.53). In group 1 positive bacteriology decreased from 74% to 24% just after surgery, and in group 2 it decreased from 90% to 10%, but this was not statistically different (Fisher's test p = 0.63). In group 1 no-one died the first month, but 8/42 (19%) died within a year; in group 2 one died within a month, and only this death (10%) within a year. This difference in case fatality was not statistically significant. Conclusions: The use of pedicle muscle flap for bronchial stump coverage during the pneumonectomies for destructive drug resistant tuberculosis can prevent severe postoperative fistulas and improve postoperative life.publishedVersio

Effect of physicochemical properties on the pharmacokinetic parameters of the new representative of benzothiazinones antituberculosis drug macozinonе

Introduction.Tuberculosis (TB) is one of the top ten causes of death worldwide. Improvement of the treatment options via development of new drugs and treatment regimens that would be more convenient for patients is one of key options of improving the effecacy of the TB prevention and careis. Since the creation of new treatment regimens by minimizing the number of the drugs used and reducing the duration of treatment is the most promising and correct direction, macozinone, a new candidate of the benzothiazinone series, can become the basis for development of new chemotherapy regimens for drug-resistant forms of TB including the combination of macozinone with the most effective modern anti-TB drugs. Aim.Comparative evaluation of the pharmacokinetic properties of macozinone capsules 80 mg and the new dosage form a dispersible tablet for preparation of oral solution. Materials and methods.Solubility of the substance macozinone in biorelevant media in vitro, permeability of macozinone in the test Caco-2 in vitro, as well as pharmacokinetics of macozinone in dogs in vivo were evaluated. Results.The solubility assessment in biorelevant media showed that the average limit of macozinone substance dissolution in the pH 5.0 acetate buffer solution was from 6 to 9 mg/l, in FaSSIF medium (fasted) from 2.5 to 4 mg/l, and in FeSSIF medium (after meals) from 16.8 to 29 mg/l. It is established that the cell permeability of the pharmaceutical substance macozinone in the CACO-2 test system is on average 2.510-6cm/s in the forward direction from the apical to basolateral cell membrane, and 1.510-6cm/s in the reverse direction, which corresponds to low permeability. The main pharmacokinetic parameters of macozinone dispersable tablets 160 mg, after dosing with food and on an empty stomach, as well as capsules 80 mg, when administered on an empty stomach in vivo studies in dogs are presented. Discussion.The specific physicochemical properties of macozinone, the problems of developing the new dosage form, as well as ways of solving some of them are presented. Conclusion.In the process of new dosage forms development, the existing chemical properties of the macozinone substance should be considered. One of the promising ways of increasing bioavailability and, consiquently, efficacy is development a fundamentally new drug form with modified release within the absorption window